5th World Congress on Cancer Therapy
Peking University Shenzhen Hospital, China
Title: Mesenchymal stem cells as carriers and amplifiers in CRAd delivery to tumors
Biography: Xia Xi
Background: Mesenchymal stem cells (MSCs) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. Th is study was to explore the distribution pattern, kinetic delivery of adenovirus, and therapeutic effi cacy of the MSC loading of E1A mutant conditionally replicative adenovirus Adv-Stat3(-) which selectively replicated and expressed high levels of anti-sense Stat3 complementary DNA in breast cancer and melanoma cells. Methods: We assessed the release ability of conditionally replicative adenovirus (CRAd) from MSC using crystal violet staining, TCID(50) assay, and quantitative PCR. In vitro killing competence of MSCs carrying Adv-Stat3(-) toward breast cancer and melanoma was performed using co-culture system of transwell plates. We examined tumor tropism of MSC by Prussian blue staining and immunofl uorescence. In vivo killing competence of MSCs carrying Adv-Stat3(-) toward breast tumor was analyzed by comparison of tumor volumes and survival periods. Results: Adv-Stat3(-) amplifi ed in MSCs and were released 4 days aft er infection. MSCs carrying Adv-Stat3(-) caused viral amplifi cation, depletion of Stat3 and its downstream proteins, and led to signifi cant apoptosis in breast cancer and melanoma cell lines. In vivo experiments confi rmed the preferential localization of MSCs in the tumor periphery 24 hours aft er tail vein injection, and this localization was mainly detected in the tumor parenchyma aft er 72 hours. Intravenous injection of MSCs carrying Adv-Stat3(-) suppressed the Stat3 pathway, down-regulated Ki67 expression, and recruited CD11b-positive cells in the local tumor, inhibiting tumor growth and increasing the survival of tumor-bearing mice. Conclusions: Th ese results indicate that MSCs migrate to the tumor site in a time-dependent manner and could be an eff ective platform for the targeted delivery of CRAd and the amplifi cation of tumor killing eff ects.